title: Safety issues in the development of treatments for osteoarthritis: recommendations of the Safety Considerations Working Group.
abstract: OBJECTIVE
  The symptomatic treatment of osteoarthritis (OA) remains to be improved, as many patients do not respond well to current palliative therapies and/or suffer unacceptable adverse events. Given the unmet need for innovative, effective and well-tolerated therapies, it is important to develop the means to estimate the ongoing safety profile of novel therapeutic agents over short- and longer term use.
  
  
  METHODS
  Methods are presented to estimate the number of serious adverse events (SAEs) of interest considered as "acceptable" per 1000 patient-years exposure and to estimate the numbers of patient-years needed in a randomized controlled trial (RCT) to meet objectives. As exposure is increased, more evidence is accrued that the overall risk is within study limits. It is equally important that requirements for delineating the safety of promising new therapies not create barriers that would preclude their development. Therefore, ongoing surveillance of occurrence of SAEs of interest during clinical development is proposed, for example after every incremental 500 patient-years exposure are accrued.
  
  
  RESULTS
  This paper and others in this special issue focus on identification of safety signals for symptomatic treatments of OA. Much less information is available for agents aimed at slowing/preventing structural progression but it is expected that a higher risk profile might be considered acceptable in the context of more promising benefit.
  
  
  CONCLUSIONS
  This paper provides a proposal and supporting data for a comprehensive approach for assessing ongoing safety during clinical development of both palliative and disease-modifying therapies for OA.
authors.affiliation: Division of Immunology and Rheumatology, Stanford University School of Medicine, Palo Alto, CA, USA. vstrand@stanford.edu
authors.forename: V
authors.initials: V
authors.lastname: Strand
authors.forename: D A
authors.initials: DA
authors.lastname: Bloch
authors.forename: R
authors.initials: R
authors.lastname: Leff
authors.forename: P M
authors.initials: PM
authors.lastname: Peloso
authors.forename: L S
authors.initials: LS
authors.lastname: Simon
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000139:chemically induced; D006801:Humans; D010003:Osteoarthritis / Q000188:drug therapy*; D017410:Practice Guidelines as Topic; D011358:Product Surveillance, Postmarketing / Q000379:methods; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012107:Research Design; D018570:Risk Assessment / Q000379:methods
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal